Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation (NCT01278745), a randomized phase 2 study. The primary outcome is Change in Percent Atheroma Volume (PAV).

2. Clinical Question

The trial asks whether rituximab induction, added to conventional immunosuppression after heart transplantation, changes the course of coronary arterial obstruction as measured by percent atheroma volume (PAV). The primary endpoint is change in PAV from baseline to 1 year, measured by intravascular ultrasound (IVUS) in a target coronary artery. The registry describes a decrease in PAV as indicating less obstruction and a better outcome.

The comparison is between a rituximab group and a placebo group. Both groups received conventional immunosuppression identified in the registry as tacrolimus, MMF, and a steroid taper. The registry record describes the participants as heart transplant recipients and identifies cardiac allograft vasculopathy as the clinical condition of interest.

The posted primary results concern randomized participants with available data at year one, rather than everyone enrolled. The mean change was 6.8 percent in the rituximab group and 1.9 percent in the placebo group. Because an increase represents more obstruction under the endpoint description, the observed direction of the means is not a decrease in PAV in either group, and the increase was greater in the rituximab group.

The clinical question is therefore about the measured difference in PAV change between these groups in the posted analysis population. The result is a comparison of an imaging measure over the stated timeframe. It does not, by itself, establish what would happen to every transplant recipient or demonstrate effects on outcomes such as survival or retransplantation.

3. Trial Design

This was a phase 2, randomized, parallel-group trial with quadruple masking, according to the registry record. The intervention comparison was rituximab induction versus rituximab placebo, with conventional immunosuppression identified as tacrolimus, MMF, and a steroid taper in both arm descriptions. The sponsor was the National Institute of Allergy and Infectious Diseases (NIAID).

The registry records an enrollment of 362. The trial start is recorded as 2011-09, and primary completion as 2015-10. Its status is listed as terminated. The reason for termination and the timing or circumstances of that decision are not reported in the registry record; the status alone does not explain why enrollment or follow-up ended.

The primary endpoint was change in PAV from baseline to 1 year, measured using IVUS. Its stated analysis population was randomized participants with available data at year one. The posted primary means are based on 49 participants in the rituximab group and 37 in the placebo group. Those endpoint counts are smaller than the overall enrollment, but the reasons for the difference and the participant flow leading to the analysis groups are not reported in the registry record.

The record lists 13 outcome measures and 12 posted secondary outcomes. The secondary outcomes include death, retransplantation or relisting, and several measures of rejection. Results are available for some, but not all, of those outcomes in the data. The registry record does not report the original sample-size justification, the planned interim analyses, or a complete statistical analysis plan. It also does not state the reason for the terminated status. These omissions limit what can be concluded about the intended design and analysis decisions.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Randomized participants with available data at year one

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Randomized participants

6. Primary Endpoint

The registry lists the primary outcome as Change in Percent Atheroma Volume (PAV), measured over Baseline, 1 year.

The primary endpoint is change in percent atheroma volume (PAV), expressed as a percent, from baseline to 1 year. PAV is a measure of the degree of coronary arterial obstruction associated with host alloimmune processes. It is measured by intravascular ultrasound (IVUS) in a target coronary artery. The registry describes a decrease in PAV as an indicator of less obstruction and a better outcome.

Using a continuous imaging measure preserves information about the magnitude of change rather than reducing each participant’s result to a category such as improved or not improved. In general, continuous outcomes can make distinctions across a range of observed measurements, although their interpretation depends on measurement quality, analysis choices, and the clinical meaning of a change. That is general statistical context, not an additional claim about this trial.

The posted primary result is a mean change, with standard deviations reported for each group. The mean change was 6.8 percent for rituximab and 1.9 percent for placebo. Both are increases, and the endpoint description gives a decrease—not an increase—as the direction indicating less obstruction. These data describe the imaging endpoint in participants with available year-one data. They do not directly measure every clinical consequence of cardiac allograft vasculopathy, and the registry record does not report a clinical threshold for interpreting the size of a PAV change.

7. Results Posted in the Registry

• Rituximab: mean 6.80 versus 1.90 on control; difference 4.90 (95% CI 2.20 to 7.60), standardized effect d = 0.72; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Death

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Rituximab: 3.4% (3/89) versus 6.8% (5/74) on control; risk difference -3.4 percentage points (95% CI -10.2 to 3.5), risk ratio 0.50 (0.12–2.02); unadjusted two-proportion z-test p = 0.319.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Rituximab and the control. The interval gives the range of effects that remain compatible with the data.

Incidence of BPAR (Any Grade)

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Rituximab: 47.7% (41/86) versus 74.3% (52/70) on control; risk difference -26.6 percentage points (95% CI -41.3 to -11.9), risk ratio 0.64 (0.49–0.83); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Rituximab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Incidence of AMR

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Rituximab: 9.0% (8/89) versus 14.9% (11/74) on control; risk difference -5.9 percentage points (95% CI -15.9 to 4.2), risk ratio 0.60 (0.26–1.42); unadjusted two-proportion z-test p = 0.244.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Rituximab and the control. The interval gives the range of effects that remain compatible with the data.

The secondary results have a mixed overall pattern rather than a uniform signal across outcomes. The unadjusted BPAR incidence comparison shows a clearer difference between groups than the death and AMR comparisons. The latter estimates are less precise, with intervals that include no difference. These outcomes concern different clinical events, so their results need not mirror the continuous PAV endpoint.

The registry’s primary endpoint is an imaging measure of PAV change. Secondary outcomes such as death, rejection, and AMR address other aspects of participant outcomes and cannot be treated as substitutes for the primary measure. A secondary result that appears more distinct does not establish that the primary finding has been confirmed, and an uncertain secondary estimate does not erase the primary result.

There are multiple secondary outcomes listed, while detailed results in the registry record cover only some of them. The record does not report a prespecified hierarchy or a method for adjusting secondary tests for multiplicity. In general, examining many outcomes without adjustment increases the chance that at least one will appear statistically notable by chance. For that reason, unadjusted secondary results carry less weight as confirmatory evidence and are more appropriately read as supporting context for the primary analysis.

The registry’s results also do not provide a complete account of the analysis populations and missing data for every secondary outcome. Different outcomes have different denominators in the posted results. The registry record does not explain all denominator differences or describe whether the same participant-level analysis rules were used throughout. The overall secondary pattern is therefore informative but incomplete, and should not be combined into a single claim about benefit, harm, or consistency across all outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Death
• Re-transplantation or Re-listed for Transplantation
• Number of Episodes of Biopsy Proven Acute Rejection (BPAR) of Any Grade Per Participant
• Incidence of BPAR (Any Grade)
• Incidence of AMR
• Incidence of Cellular Rejection
• Incidence of Any Treated Rejection
• Number of Participants With Episodes of Rejection Associated With Hemodynamic Compromise (HDC)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is continuous: each participant’s PAV change is a numeric measurement, and the group summaries are means with standard deviations. A mean represents the central value of the measurements, while a standard deviation describes how spread out participant measurements are around that mean. General statistical context: the standard deviation describes variation among individual observations; it is not the same as the uncertainty in the estimated group mean.

What does the unadjusted comparison express?

The recalculated mean difference is the rituximab group mean minus the placebo group mean. Its value is 4.9 percentage points. Since the endpoint is change in PAV, a positive difference means the average change was larger in the rituximab group. The endpoint description gives a decrease in PAV as the direction indicating less obstruction, so the sign of the difference must be interpreted in that context rather than as inherently beneficial or harmful.

This recalculation uses the posted group means, standard deviations, and sample sizes to form an unadjusted comparison. It does not incorporate covariates or reproduce the registry’s ANCOVA analysis. The recalculated interval, from 2.203 to 7.597, expresses uncertainty around that unadjusted mean difference under the calculation used. Its confidence level is not stated in the primary-result information in the registry record, so a confidence percentage should not be assigned to it.

How should the p-values be read?

A p-value is a measure of how compatible observed data are with a specified null model, under the assumptions of the analysis. General statistical explanation: a small p-value can indicate that the data would be unusual under a model of no group difference, but it is not the probability that the null model is true, nor does it measure clinical importance. The unadjusted recalculation gives p < 0.001; the registry’s ANCOVA analysis reports p = 0.002. The registry record does not provide the ANCOVA estimate or interval, and the analyses should remain distinguished.

The registry names ANCOVA as its reported method. In general, analysis of covariance compares outcomes while accounting for one or more covariates. The registry record does not identify the covariates included, the model specification, or whether the ANCOVA used the change score or another outcome formulation. Those details should not be inferred from the method label alone.

Why do the analysis populations matter?

The primary analysis population is described as randomized participants with available data at year one. The primary endpoint summaries include 49 participants in the rituximab group and 37 in the placebo group, while the overall enrollment is 362. The record does not provide a complete accounting of participants from enrollment through randomization and endpoint availability. It also does not explain missing primary measurements or report a missing-data method. Consequently, the reported comparison describes the available-data group summaries, and the extent to which missing data could alter the result is not reported in the registry record.

Randomization is intended, in general, to make treatment groups comparable at allocation. It does not automatically resolve bias introduced after randomization by missing outcomes, departures from assigned treatment, or selective reporting. The record does not give enough detail to assess those issues fully. Likewise, quadruple masking is recorded, but the identities of the four masked parties and the procedures used to maintain masking are not reported in the registry record.

Why do secondary results need caution?

The registry lists multiple secondary outcomes. When many outcomes are examined, the chance of finding at least one apparently noteworthy result can rise if no adjustment is made for the set of tests. General statistical explanation: multiplicity procedures can control or otherwise address that issue, but the registry record does not report a multiplicity adjustment or a prespecified hierarchy for the secondary analyses. The posted secondary p-values are therefore best treated as unadjusted evidence, not as a definitive set of independent confirmations.

Some secondary estimates are binary comparisons, such as whether a participant had a reported event. For a risk difference, the estimate contrasts the proportions in the two groups; an interval spanning zero is compatible with no difference under that measure. The primary endpoint, by contrast, is a continuous change in PAV. Results from different outcome types answer different questions and should not be merged into a single overall effect.

The planning illustrations use the observed effect as a reference and report participants per arm for selected fractions of that effect. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. General statistical explanation: planning calculations are sensitive to the assumed effect and variability, and a smaller target effect generally requires more participants to detect with a chosen power. These illustrations are not the trial’s original sample-size design, whose assumptions are not reported in the registry record.

11. Confidence Intervals and Precision

Precision concerns how narrowly the data locate an estimated group difference. The recalculated primary mean difference is 4.9 percentage points, with an interval from 2.203 to 7.597. The interval lies on the positive side of zero, indicating that the unadjusted estimate is not merely a point estimate of a difference in either direction. Its width also shows that the exact size of the mean difference remains uncertain.

General statistical explanation: a confidence interval is a range generated by a statistical procedure to express uncertainty in an estimate. A narrower interval indicates greater precision under the assumptions of that procedure; a wider interval indicates less precision. The registry record does not report the confidence level for the primary recalculated interval, so the interval should not be labeled with a confidence percentage based on the information available.

The primary endpoint groups have standard deviations of 8.21 and 4.38, respectively. These describe variation among participant measurements, not the width of the interval for the group difference. The primary analysis includes 49 rituximab participants and 37 placebo participants with available year-one data. The interval reflects the reported summary-statistic comparison, but does not account for unknown effects of missing data or establish that the available-data population represents all randomized participants.

The sponsor’s ANCOVA result is reported with p = 0.002, but its effect estimate and interval are not reported in the registry record. Its precision and magnitude therefore cannot be assessed from the p-value alone. The secondary comparisons also have varying precision: some intervals are broad, and the death and AMR intervals include zero. Overall, precision should be judged from the estimate and interval together, and not from statistical significance alone.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning illustrations report participants per arm for the continuous primary outcome and the binary secondary outcomes. They do not report total event counts. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The calculations use the observed effect as a reference and consider planning for 100%, 75%, and 50% of that observed effect.

The 80% power column gives the illustrative number of participants per arm needed for an analysis to have 80% power under those assumptions and the selected target effect. The 90% power column gives the corresponding per-arm number for 90% power. In general, power describes the probability of detecting an effect of the specified size under the planning model when that effect is present. A higher target power generally requires more participants, and a smaller target effect requires more participants because it is harder to distinguish from random variation.

These are planning illustrations based on observed results, not the trial’s original design calculations. The registry record does not report the original sample-size justification or its assumptions. The figures are not observed power: they do not measure the probability that this completed trial detected its actual effect. They are hypothetical planning quantities that depend on the stated assumptions and the chosen fraction of the observed effect.

The observed endpoint counts and the planning counts answer different questions. The primary analysis has 49 participants in the rituximab group and 37 in the placebo group with available data at year one. Those are observed analysis counts; the planning entries are not a description of the enrollment or of the number actually analyzed.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 4.900; pooled standard deviation σ = 6.837.
2. n = 2 × (1.96 + 0.842)² × 6.837² / 4.900² = 30.6, rounded up to 31 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 4.9                      # observed difference in means
sigma <- 6.83655719538089                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1278745)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 31 (80% power), 41 (90% power)
 75% of observed effect: n per arm = 55 (80% power), 73 (90% power)
 50% of observed effect: n per arm = 123 (80% power), 164 (90% power)
power.t.test: 31.5 
Simulated power at n = 31 per arm: 0.794 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s reported primary analysis is ANCOVA, with p = 0.002. The registry record does not provide an ANCOVA effect estimate, interval, covariate list, or fuller model specification. The sponsor’s result therefore supplies evidence from the named analysis, but its effect magnitude and precision cannot be reconstructed from the reported p-value alone.

The recalculated comparison is an unadjusted difference between the posted group means. It is 4.9 percentage points, with an interval from 2.203 to 7.597 and p < 0.001. This calculation is useful as a transparent comparison of the posted summary statistics, but it is not a reproduction of ANCOVA and should not be presented as the sponsor’s analysis.

The two analyses point to a statistically discernible group difference, but their p-values should not be compared as though they were generated by the same model. Since the registry does not report the sponsor’s estimate or interval, the magnitude and uncertainty of the ANCOVA contrast remain not reported in the registry record. The posted means indicate the direction of the unadjusted difference; interpretation of the sponsor’s precise contrast is limited by the missing estimate and model details.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures and 12 secondary outcomes, indicating that the trial considered multiple endpoints. The registry record does not report whether the primary endpoint was formally protected as the sole confirmatory test, whether secondary outcomes had a prespecified testing order, or whether any multiplicity adjustment was used. Without those details, the statistical status of the secondary findings is difficult to assess beyond their individual estimates and unadjusted comparisons.

General statistical explanation: when many hypotheses are tested, a result can appear statistically notable by chance even if there is no true difference for any of them. Adjusting for multiplicity or specifying a hierarchy can help control how results are interpreted. The absence of a reported method does not establish that no method was used; it means the method is not reported in the registry record. The secondary findings should therefore not be treated as a set of independent confirmatory tests.

The primary analysis population is described as randomized participants with available data at year one. The registry record does not report a full participant flow, reasons for missing primary measurements, or a missing-data sensitivity analysis. It does not state whether the primary analysis followed an intention-to-treat principle or how participants with missing outcomes were handled. Those omissions make it difficult to determine whether the available-case comparison could be affected by selective outcome availability.

The endpoint sample sizes differ from the overall enrollment, and secondary outcomes have their own denominators. The record does not provide enough detail to explain all of those differences or to determine whether missingness was related to assigned group, participant characteristics, or outcomes. Such relationships can affect the interpretation of an available-data result, but their presence or absence cannot be inferred from the reported counts.

The trial is listed as terminated, but the reason for termination and any consequences for planned analyses are not reported in the registry record. The original sample-size justification, interim analyses, and full statistical analysis plan are also not reported. These gaps limit assessment of whether the reported analyses followed the original plan and how firmly the findings were intended to be interpreted.

16. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: transplant rejection (13.5%), pneumonia (8.1%), renal failure acute (6.7%), neutropenia (3.4%), coronary artery disease (3.4%).

The registry reports serious adverse events among 89 participants in the rituximab group and 74 in the placebo group. Serious adverse events affected 55 and 45 participants, respectively. Other adverse events affected 29 participants in the rituximab group and 26 in the placebo group. The registry also lists participants discontinued before transplant and before randomization; those groups are distinct from the randomized treatment arms and should not be combined with them when interpreting the arm-specific figures.

The listed serious adverse event terms include transplant rejection at 13.5%, pneumonia at 8.1%, renal failure acute at 6.7%, neutropenia at 3.4%, coronary artery disease at 3.4%, and gastroenteritis at 3.4%. The registry record does not provide enough detail in these figures to establish whether each percentage refers to participants or events, or to define the denominator for each term. Death counts are not reported in the adverse-event summary.

These counts describe events recorded in the registry, not proof that an event was caused by either assigned intervention. The available figures do not by themselves support a complete safety comparison, particularly without fuller definitions, follow-up details, and an explanation of the event denominators.

17. What the Result Does, and Does Not, Mean

The primary posted results show a larger mean increase in PAV among participants assigned to rituximab than among those assigned to placebo, in the available-data analysis at year one. The unadjusted recalculated mean difference is positive, and its interval is on the positive side of zero. The registry’s own ANCOVA analysis reports p = 0.002, but does not report its effect estimate or interval.

This is a statistical description of a group-level imaging outcome. It does not establish the clinical importance of the observed difference: the registry record does not report a threshold for a meaningful PAV change. It also does not show that every participant experienced the group average, nor does it identify what would happen to a particular person.

The endpoint is a measure of coronary arterial obstruction, not a direct measure of every consequence of cardiac allograft vasculopathy. The posted primary result does not by itself establish an effect on survival, retransplantation, or other clinical outcomes. Those outcomes have separate results, and some secondary comparisons are uncertain. The registry record also does not report results for every listed secondary outcome.

The analysis population includes randomized participants with available year-one data. Because the reasons for missing primary measurements and the full participant flow are not reported, the extent to which the available cases represent all randomized participants cannot be assessed from the record. The terminated status likewise does not explain the trial’s course or the reason results are limited.

In general, statistical evidence and clinical interpretation are related but distinct. A small p-value does not quantify the importance of a difference, and an interval does not resolve design or missing-data limitations. The results should be read as evidence about the measured comparison in the reported analysis population, with uncertainty and reporting limitations, rather than as a universal conclusion about rituximab or heart transplantation.

18. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition, direction, analysis population, and statistical model all matter when reading a clinical result. PAV is an imaging measure for which the registry identifies a decrease as the direction indicating less obstruction. The posted means are increases in both arms, with a larger mean increase in the rituximab group. Reading the sign of the comparison alongside the endpoint’s clinical direction prevents a statistical difference from being mistaken for improvement.

It also demonstrates the distinction between a registry-reported analysis and an unadjusted recalculation from group summaries. The registry names ANCOVA and reports p = 0.002, whereas the recalculation compares the posted means and standard deviations. The estimates and p-values arise from different analysis approaches, and the registry does not provide enough ANCOVA detail to reconstruct its estimate or precision.

The primary analysis includes only participants with available year-one data, while the total enrollment is 362. Without a participant flow or explanation of missing outcomes, readers cannot fully judge how the analysis population relates to enrollment. This is a statistical limitation, not a basis for assuming a particular pattern of missingness.

Finally, the record lists multiple secondary outcomes and a terminated status, but does not report a complete multiplicity strategy, the reason for termination, or the original design assumptions. These gaps show why registry results are most informative when their estimates are read together with analysis details, uncertainty, and the boundaries of what was reported.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to the information recorded for this trial. The overall enrollment is 362, but the primary endpoint summaries include 49 participants in the rituximab group and 37 in the placebo group. The registry describes the primary population as randomized participants with available data at year one, but does not provide a complete participant flow or reasons why primary endpoint data are unavailable for others.

The sponsor’s primary analysis is identified as ANCOVA and has a reported p-value, but its estimate, interval, covariates, and fuller model specification are not reported in the registry record. The unadjusted recalculation can therefore provide a direct summary-statistic comparison but cannot reproduce or fully interpret the sponsor’s model.

The trial status is terminated, and the reason is not reported. The record also does not report the original sample-size justification, interim analyses, or a complete statistical analysis plan. These omissions prevent assessment of whether the final analysis followed all planned procedures or whether trial termination affected the intended analysis.

The registry lists multiple secondary outcomes, but results for all listed measures are not available in the reported data. A multiplicity approach is not reported. The serious adverse event terms are accompanied by percentages, but the event-specific denominators and whether percentages refer to participants or events are not clear in the record. These reporting limitations constrain comparisons and should not be filled in by assumption.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation — NCT01278745.
• Registry record last updated 2026-09-24; status last verified 2026-09.
• Results first posted 2017-04-11.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

The registry record describes a randomized, quadruple-masked, parallel-group phase 2 trial sponsored by NIAID, with enrollment of 362 and status listed as terminated. It compares rituximab induction with placebo, alongside conventional immunosuppression, in heart transplant recipients.

The primary endpoint is change in PAV from baseline to 1 year, measured by IVUS. Among randomized participants with available year-one data, the mean change was 6.8 percent for rituximab and 1.9 percent for placebo. The registry reports an ANCOVA p-value of 0.002; the unadjusted recalculated mean difference is 4.9 percentage points, with an interval from 2.203 to 7.597 and p < 0.001.

The registry record does not report the original sample-size justification, reasons for termination, a complete participant flow, or a complete statistical analysis plan. Those gaps limit assessment of missing data, multiplicity, and the relation between the posted analyses and the original design.